Evidence map›Paper›PMID 34788599›Full record

ArticleImmunity2021

Vaccination in a humanized mouse model elicits highly protective PfCSP-targeting anti-malarial antibodies.

Sven Kratochvil, Chen-Hsiang Shen, Ying-Cing Lin, Kai Xu, Usha Nair, Lais Da Silva Pereira, Prabhanshu Tripathi, Johan Arnold, Gwo-Yu Chuang, Eleonora Melzi and 23 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
5.5field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 46 citations in OpenAlex.

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  10. Machine learning enables de novo multiepitope design ofProceedings of the National Academy of Sciences of the United States of America · 2025
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  14. iScience · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors at 5 institutions in 1 country.

Sven KratochvilThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Chen-Hsiang ShenVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Ying-Cing LinThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Kai XuVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Usha NairThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Lais Da Silva PereiraVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Prabhanshu TripathiVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Johan ArnoldThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Gwo-Yu ChuangVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Eleonora MelziThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Arne SchönDepartment of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
Baoshan ZhangVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Marlon DillonVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Brian BonillaVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Barbara J FlynnVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Kathrin H KirschThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Neville K KisaluVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Patience K KiyukaVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Tracy LiuVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Li OuVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Marie PanceraVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA; Vaccine Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Reda RawiVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Mateo ReveizVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Kareen SeignonThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Lawrence T WangVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Michael T WaringThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
John WarnerThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Yongping YangVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Joseph R FrancicaVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Azza H IdrisThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Robert A SederVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rseder@nih.gov.
Peter D KwongVaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pdkwong@nih.gov.
Facundo D BatistaThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA; Department of Microbiology, Harvard Medical School, Boston, MA, USA. Electronic address: fbatista1@mgh.harvard.edu.
National Institutes of Health · USRagon Institute of MGH, MIT and Harvard · USHarvard University · USHoward Hughes Medical Institute · USJohns Hopkins University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
Neutralization Mechanisms Of Anti-HIV-1 Monoclonal AntibodiesZIAAI005022 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$24.6M
Development of Pre-Erythrocytic Malaria Vaccines and antibodiesZIAAI005107 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SEDER, ROBERT A · 2010 to 2025
$20.7M
Intramural NIH HHS ZIA AI005022Intramural NIH HHS ZIA AI005107NIGMS NIH HHS T32 GM007198
6 · The paper itself

Abstract

Repeat antigens, such as the Plasmodium falciparum circumsporozoite protein (PfCSP), use both sequence degeneracy and structural diversity to evade the immune response. A few PfCSP-directed antibodies have been identified that are effective at preventing malaria infection, including CIS43, but how these repeat-targeting antibodies might be improved has been unclear. Here, we engineered a humanized mouse model in which B cells expressed inferred human germline CIS43 (iGL-CIS43) B cell receptors and used both vaccination and bioinformatic analysis to obtain variant CIS43 antibodies with improved protective capacity. One such antibody, iGL-CIS43.D3, was significantly more potent than the current best-in-class PfCSP-directed antibody. We found that vaccination with a junctional epitope peptide was more effective than full-length PfCSP at recruiting iGL-CIS43 B cells to germinal centers. Structure-function analysis revealed multiple somatic hypermutations that combinatorically improved protection. This mouse model can thus be used to understand vaccine immunogens and to develop highly potent anti-malarial antibodies.

Indexed as

Adoptive TransferAnimalsAntibodies, ProtozoanB-Lymphocyte SubsetsDisease Models, AnimalEpitopesGenetic EngineeringHumansImmune EvasionImmunogenicity, VaccineMalariaMalaria VaccinesMiceMice, SCIDPlasmodium falciparumProtozoan ProteinsAntibodies, Protozoancircumsporozoite protein, ProtozoanEpitopesMalaria VaccinesPfCSP DNA vaccineProtozoan ProteinsVaccines, DNAadoptively transferred B cellsantibody CIS43circumsporozoiteepitope-focused immunizationin situ vaccinationjunctional epitopemalariapassive protectivePfCSP

Identifiers

PMID34788599
PMCPMC9087378
OpenAlexW3213650492

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.